The molecular mechanism of T1AM on weight maintenance and reversing obesity

The aim of this study aspect was to test the effect of an acute short term pharmacological dose of T1AM in vivo on weight loss, fat loss, and shifts in metabolic substrate utilization from carbohydrate (CHO) to lipid and to compare T1AM’s effects in these areas along side it’s structural analogs (TH, SG-2), synthetic metformin (MET) drug therapy, and route of administration (oral gavage vs. injection). To provide this comparison T1AM, MET, TH, and SG-2 treatments were administered acutely in CD-1 mice to assess their impact on body mass, metabolic substrate utilization, metabolite profile, and gene expression. Study treatments did not result in changes to body mass compared to controls, however T1AM, MET, TH, and SG-2 treatments resulted in significant shifts towards fatty acid utilization as indicated by decrease δ13CO2 in expired breath measured by cavity ring-down spectroscopy analysis. Plasma metabolite analysis for the most part did not reveal any significant changes due to T1AM treatment but more so from TH treatment in glucose, insulin, and triglycerides. T1AM treatment showed divergent responses in gene expression as well as δC13 values between routes of administration when comparing intraperitoneal administration to oral gavage. The effects of acute administration of high dosage T1AM do not appear as robust as those seen previously with low chronic dosages and that this response may differ dramatically with route of administration.